chelating agents

Summary

Summary: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy protocols.

Top Publications

Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease

Aftab AlaUCL Institute of Hepatology, Hampstead Campus, Division of Medicine, Royal Free and University College Medical School, University College London, London, UKLancet 369:397-408. 2007

Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments

..Based on evidence from the studies reviewed herein, trientine is now proceeding into the later stages of pharmaceutical development for the treatment of heart failure and other diabetic complications...

Aftab AlaUCL Institute of Hepatology, Hampstead Campus, Division of Medicine, Royal Free and University College Medical School, University College London, London, UKLancet 369:397-408. 2007

..There are several chelating agents and zinc salts for medical therapy...

Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments

..Interestingly, addition of Ca(2+), or Mg(2+) had no effect. The antioxidant N-Acetyl-L-Cysteine inhibited the cytotoxic effect of DTPA and TPEN, indicating that oxidative stress is the likely mediator of Zn-deficiency-related cell death...

Fast growth increases the selective advantage of a mutation arising recurrently during evolution under metal limitation

..There was a suggestion that sevelamer was associated with lower overall, but not cardiovascular-linked, mortality in older patients. We suggest that further research is needed to confirm these findings...

..Copper and zinc homeostasis in brain and age associated changes are then outlined, along with a discussion of the possible involvement of Zn, Cu and Fe in Alzheimer's disease. We conclude with a brief summary of chelation therapy in AD...

Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients

..In tumor models, the copper-chelating agent tetrathiomolybdate (TM) has been shown to be antiangiogenic. We evaluated the antitumor activity of TM in patients with hormone-refractory prostate cancer (HRPC)...

..The trial is designed to have >85% power to detect a 25% relative reduction in the primary end point for each treatment factor. Enrollment began in September 2003 and was completed in October 2010...

..A combination of lipid-lowering and anti-inflammatory effects along with avoidance of hypercalcemia should be taken into account when choosing phosphorus binders for maintenance hemodialysis (MHD) patients...

The copper chelator, D-penicillamine, does not attenuate MPTP induced dopamine depletion in mice

..Together, these results suggest that cellular effects of biguanides depend on their metal-binding properties. This link may illuminate a better understanding of the molecular mechanisms enabling antihyperglycemic drug action...

..Current research is directed towards finding naturally-occurring antioxidants of plant origin. The aim of the present study was to evaluate the in vitro antioxidant activities of Spondias pinnata stem bark extract...

..Such cellular DNA breakage is inhibited by copper specific chelator but nor by iron or zinc chelating agents. Similar results are obtained with isolated nuclei indicating that chromatin bound copper is mobilized in ..

Chelating agents in root canal treatment: mode of action and indications for their use

..in brain lead concentration in animals administered LA plus thiol chelators, compared to the effects of chelating agents alone. This is an interesting and notable observation, which requires further exploration...

Effects of chelating agents and sodium hypochlorite on mineral content of root dentin

..These observations show that by inducing a rapid increase in cytosolic free Ca2+, cyanide can partially initiate the apoptotic cascade through a calcineurin-mediated translocation of Bad to mitochondria...

..These findings further suggest that a bifunctional chelator derivative of CB-TE2A is a highly desirable alternative for labeling copper radionuclides to biological molecules for diagnostic imaging and targeted radiotherapy...

..Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity...

..Therefore, TAM receptor activation and regulation can independently influence both oligodendrocyte survival and the microglial response after CNS damage...

Examination of the antiproliferative activity of iron chelators: multiple cellular targets and the different mechanism of action of triapine compared with desferrioxamine and the potent pyridoxal isonicotinoyl hydrazone analogue 311

..This compound is a potential Fe chelator, but despite this, no investigations have examined its effect on cellular Fe metabolism. This is essential for understanding its mechanism of action and clinical effects...

..Our results show that clioquinol has anticancer effects both in vitro and in vivo. Transition metal ionophores may be a subclass of metal chelators with anticancer activity deserving of further development...

A copper(II)-selective chelator ameliorates diabetes-evoked renal fibrosis and albuminuria, and suppresses pathogenic TGF-beta activation in the kidneys of rats used as a model of diabetes

..Here, we report the effects of TETA treatment on Cu and other essential elements, as well as on indices of renal injury and known pathogenic molecular processes, in kidneys from a rat model of diabetes...

..Few controlled studies have addressed interventions to reduce VC but non-calcium-based phosphate binders may be beneficial. No published randomized study to date has assessed the effect of lanthanum carbonate (LC) on VC progression...

..EGTA and H-EDTA have small binding rate constants for calcium in the range of 3 x 10(6) M-1s-1 since, at pH 7.20, protons need to be dissociated from the chelators before they can bind calcium ions...

..These findings indicate that LC binds phosphate more effectively than SH across the pH range encountered in the gastrointestinal tract, and has a lower propensity for bound phosphate to be displaced by competing anions in the intestine...

The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system

Iwao OhnoDivision of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, TokyoIntern Med 48:415-20. 2009

..In this study we verify the urate-lowering effect of sevelamer in Japan in which the hemodialysis environment is different from that of western countries, and we also clarify the urate-lowering mechanism of sevelamer...

MRP2 and the DMPS- and DMSA-mediated elimination of mercury in TR(-) and control rats exposed to thiol S-conjugates of inorganic mercury

..However, as sevelamer carbonate does not decrease serum bicarbonate levels, it may be more appropriate for patients at risk for metabolic acidosis who require phosphate binders that do not contain calcium or aluminum...

..Non-adherence to phosphate binding (PB) medication may play a role in the difficulty in achieving the targets for phosphorus. We have a wide armamentarium of PB but preferences of patients are poorly understood...

..Oxidative status profile was carried out at the beginning and after 6 months' EDTA chelation. At the end of the treatment, the patient did not show any signs of metal intoxication, RA symptoms and oxidative status improved...

A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer

..TM can be safely added to IFL without compromising dose intensity or diminishing the expected RR. Changes in serum VEGF, IL-8, and IL-6 after treatment may directly reflect changes in CRC tissue angiogenesis...

..In conclusion, the positioning of the DOTA chelator influences the cellular processing and the biodistribution pattern of radiolabeled affibody molecules, creating preconditions for imaging optimization...

Managing chronic inflammation in the aging diabetic patient with CKD by diet or sevelamer carbonate: a modern paradigm shift

..If larger and longer studies confirm the hypothesis that one or both of these interventions reduce progression of CKD, it could represent a new paradigm in the management of complications in the type 2 diabetes patient with CKD...

Pharmacokinetics, pharmacodynamics, and metabolism of triethylenetetramine in healthy human participants: an open-label trial

..Based on these data, NAT2 phenotype does not affect TETA's pharmacokinetic, pharmacodynamic, or safety profiles. TETA may be acetylated via an alternative mechanism, such as that catalyzed by spermidine/spermine N(1)-acetyltranferase...

Effect of metal chelating agents on the direct and seizure-related neuronal death induced by zinc and kainic acid

G J LeesDepartment of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Auckland, New ZealandBrain Res 799:108-17. 1998

The ability of metal chelating agents to affect seizure-induced neuronal death caused by intra-amygdaloid injections of kainic acid was investigated...

Combined administration of oxalic acid, succimer and its analogue for the reversal of gallium arsenide-induced oxidative stress in rats

..Phosphate binders are widely used to control serum phosphorus levels in patients with chronic kidney disease (CKD). We analyzed the effects of phosphate binders on biochemical and patient-level end points in patients with CKD...

Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex

..Affected children may be entirely asymptomatic and the diagnosis problematic. Herein we present the clinical and laboratory characteristics of 57 children with WD and point out the diagnostic difficulties in a pediatric population...

..The aim of this crossover study was to compare the reduction of serum phosphorus (SP) with fixed doses of the non-calcium-containing phosphate binders lanthanum carbonate (LC) and sevelamer hydrochloride (SH) in hemodialysis patients...

..To enable widespread use of (89)Zr-immuno-PET, we now introduce the novel BFC p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) and compare its performance in (89)Zr-immuno-PET with the reference BFC TFP-N-sucDf...

..These findings also agree with the few experimental and human studies published. This case study points to the need for an accurate occupational history collection and suggests the possibility of useful chelating therapy with CaNa2EDTA...

..A successful agent will be highly useful invention not only for early detection of but also for following disease progression and as biomarker for assessing disease-modifying treatments for Alzheimer's disease. ..

..My project proposes to better understand the role of iron mobilization from lysosomes to mitochondria in ischemia/reperfusion injury and to develop novel therapies to mitigate or eliminate damage from this condition. ..

..Finally, we propose formal collaboration with the Thalassemia clinical research network of the National Heart, Blood, and Lung Institute, to leverage the ongoing longitudinal screening in both networks. ..

..With the acquired insight it should be possible to design drugs that specifically target pathological Zn2+ signals that may cause AD while minimally disturbing the Zn2+ signals necessary for normal brain functioning. ..

..compounds that promote Hg-C bond cleavage in vivo, and which may be used in conjunction with traditional chelating agents. Both of these approaches are important because they represent significant advances over the methods ..

..These findings will provide information in the search for alternative therapeutic approaches that are hopefully more effective and efficient to treat HIV-1. Iron chelators could add to improve the treatment of HIV disease. ..

..Achieving these specific aims will further define the role of iron in the establishment and progression of mucormycosis and define possible novel therapeutic strategies that can be applied concurrently against the disease. ..

..Since iron is increasingly suspected of having a role in inflammatory and neoplastic diseases of skin, this new information should assist in devising preventative and treatment measures for those types of diseases. ..

..The goal of this work is to provide a fundamental understanding of two enzymes that promote virulence in P. aeruginosa so that this information can be exploited to generate new antimicrobial drugs. ..

..In the proposed studies we will test this hypothesis in cell models, and investigate whether iron chelation can be used as a therapeutic measure to alleviate prion disease associated neurotoxicity. ..

..to reduce the dramatic health consequences of internal actinide/lanthanide contamination is treatment with chelating agents that form excretable complexes, although fission product lanthanides and the actinides are among the most ..

..The goal of this work is to provide a fundamental understanding of four enzymes that promote virulence in P. aeruginosa so that this information can be exploited to generate new antimicrobial drugs. ..

..The formulation will be easier and safer to administer than Desferal(R). If LDFO is validated, it would be a significant advance for the clinical treatment of transfusional iron overload in pediatric patients. ..

..He also proposes to generate antibodies against specific dicarboxylic acid containing phospholipids. He will then determine whether such antibodies react against epitopes in oxidized LDL, plasma and atherosclerotic plaques. ..

..Understanding the mechanism by which Ca2+ influences release of neurotransmitter will contribute to an improved understanding of synaptic function in general and when transmission is disrupted in disease states. ..

..proposal will develop and evaluate novel biocompatible nanomaterials that will lead to a breakthrough in the field of chelation therapies of the above heavy metals by substantially outperforming the current FDA-approved chelating agents.

The removal of certain internal radioactive contaminants can be accomplished by administering chelating agents that can preferentially complex with radionuclides in the body and increase their rate of clearance, thereby decreasing ..